Molecular events which couple a hemodynamic burden to long-term modifications of myocardial structure and function produce not only hypertrophic growth of cardiac myocytes, but also plasticity in an ensemble of cardiac gene products. Whether these genetic responses signify a purely adaptive response or, instead, a shared regulatory program is controversial. Induction of nuclear oncogenes during cardiac hypertrophy has suggested functional homology between mechanisms for growth factor signalling and transduction of mechanical stress. We have shown, in addition, that cardiac myocytes are targets for the action of peptide growth factors found in myocardium, suggesting an autocrine or paracrine model of hypertrophy. Tissue-specific genes in cardiac myocytes possess a continuum of responses to basic fibroblast growth factor (FGF) which corresponds accurately to the selective up-regulation of "fetal" genes during pressure-overload. Second, despite shared effects on 5 other cardiac genes, acidic and basic FGF differentially regulate transcription of cardiac and skeletal alpha-actin. Thus, FGF control of cardiac gene expression displays specificity and discrimination unlike that reported in other systems. In this application, we propose to: [1] Define cis-acting sequences that control the antithetical regulation of skeletal alpha-actin in cardiac myocytes by basic and acidic FGF. [2] Overexpress in cardiac myocytes a set of cellular oncogenes implicated in growth factor signal transduction, to establish whether they suffice to transactivate or trans- repress the SkA promoter. [3] Disrupt signal transduction by fos and jun proteins in cardiac proteins mediate growth factor control of the SkA promoter. [4] Utilize mutations in acidic FGF which abolish mitotic activity (but suffice for receptor binding and tyrosine phosphorylation) to delineate structural requirements for control of SkA and "downstream" cardiac genes by acidic FGF. [5] Determine the temporal expression, spatial localization, and cellular distribution of FGFs and FGF receptor in myocardium following an experimental hemodynamic load.